Each year 40,000 to 70,000 individuals are hospitalized for burn related injuries, and of this number between 6,400 and 11,200 have severe burns covering at least 20% of the person's total body surface area (BSA). Twenty years ago burns covering half of a person's BSA were fatal. However, due to medical advances, patients with 90% BSA burned are now surviving these injuries Serious burns damage the skin, requiring, in many cases, excising the damaged tissue and subsequent skin grafting. Increases in skin blood flow and sweating are critical responses for humans to appropriately regulate internal temperature during physical exertion and/or hyperthermic exposure. However, findings from the principal investigator and others show that vasodilatory and sweating responses in grafted skin are impaired or absent regardless of the maturity of the graft. Thus, patients with large areas of grafted skin may have reduced thermal tolerance. This important question has not been adequately addressed as it remains unknown to what extent skin grafting impairs the regulation of internal temperature, or whether heightened vasodilator and sweating responses from non-injured skin can compensate for reduced heat dissipating capacity of grafted skin. Thus, the first objective of this project is to test the hypothesis that subjects with 20-35% of BSA grafted skin will have normal thermoregulatory responses, subjects with 40-55% BSA grafted skin will have moderately impaired thermoregulatory responses, and subjects with >60% BSA grafted skin will have severely impaired thermoregulatory responses when compared to non-grafted subjects. It is unknown whether individuals with substantial BSA of grafted skin can adapt to elevated temperature climates and thereby reduce their risk of a heat-related injury. Heat acclimation is a widely accepted approach to improve temperature regulation in individuals required to work (i.e., firefighters or military personnel), or who choose to exercise, in hot environmental conditions. It may be that heat acclimation is effective in improving temperature regulation of individuals with skin grafts over large portions of their body. To this end, the second objective of this project is to test the hypothesis that heat acclimation improves temperature regulation of individuals with varying BSA of grafted skin. Answers to the proposed questions, as well as related mechanisms, will be pursued using novel techniques to assess both central and peripheral control of thermoregulatory efferent variables. The academic environment in which this work will be conducted is unique in that surgeons and rehabilitation physicians, who treat skin graft patients, will collaborate with investigative physiologists to address these important questions. The information gained from the proposed studies will be valuable to clinicians, patients, and the military towards an understanding of the effects of serious burn injuries and subsequent skin grafting on human temperature regulation, and whether heat acclimation will allow these individuals to better tolerate a hyperthermic challenge and thus improve thermal safety and comfort. PUBLIC HEALTH RELEVANCE: Grafted skin has impaired capability to increase skin blood flow and sweating and thus individuals with a large portion of their body having grafted skin may have compromised temperature regulatory capacity; although this has not been confirmed. The overall objectives of the proposal are to identify the extent by which skin grafting impairs temperature regulation and to investigate whether heat acclimation improves temperature regulation. The information gained from the proposed studies will be valuable to clinicians, patients, and the military towards an understanding of the effects of serious burn injuries and subsequent grafting on human temperature regulation, and whether heat acclimation will allow these individuals to better tolerate a hyperthermic challenge and thus improve thermal safety and comfort.